Biotech – The Cutting Edge: peak policy and is RNA the new DNA?

On a week where many were distracted by the FTSE c2% one-day gain (the 100/250 were on a YTD low) following the better-than-expected US inflation print (3%, the slowest rate in more than 2 years), there was also something, potentially, much more seismic for UK markets: reforms coming down the pipe for UK capital markets. We also spend time looking at messenger RNA (mRNA) and its applications away from vaccines (eg coronavirus), how CRISPR (gene editing) is being touted as the solution to everything, and note other bits going on in the news such as whether the FDA Adcomms will become a thing of the past and Illumina’s record fine for ignoring the EU.

Policy with some potential? Aside from some training (which I’m sure many of us are having to do) on the FCA’s new Consumer Duty and the Chancellor’s plans to potentially roll back MiFIDII (we’ll leave others to opine on this properly, but it feels to us a bit like trying to unscramble an omelette), many in Healthcare are talking about Jeremy Hunt’s other comments in the Mansion House speech: planned changes to unlock capital in pension funds (some £75bn). The fact that this cash (well c£50bn of it) from defined contribution schemes will be ‘voluntarily’ directed (to the tune of >5% of funds by 2030, from the current of c0.5%*) to high growth and unlisted equities is exciting stuff for Healthcare and Life Sciences. We also note – missed by many – that ‘unlisted’ for the purposes of this agreement is set to include AIM (and indeed Aquis) stocks. We think this might just be the jump start that UK Healthcare and Life Sciences need, especially as many are starting to realise that the US isn’t necessarily the land of milk and honey for all things Healthcare.

mRNA’s scope beyond vaccines. Scientific progress in gene editing has accelerated since the fight against the Covid-19 pandemic. Notably, because of mRNA technology which was used in both the Pfizer-BioNTech/Moderna vaccines. Importantly mRNA’s use is not just limited to vaccines, and there are two great examples this week. The first example is its use in a diagnostic lung cancer blood test from Hummingbird Diagnostics and the results from the non-invasive cancer blood test known as miLung are promising. The test was capable of detecting cases of lung cancer in c.85% of patients from a cohort moderate to heavy smokers (age 55 – 74). This test specifically focuses on ‘plucking’ microRNA (that can bind with mRNA to form proteins) generated by tumour cells.

The second example is mRNA’s use in a CAR-T therapy, instead of using the traditional DNA packed in a viral vector approach. The early proof of concept studies are encouraging and suggest these mRNA CAR-T’s are more well tolerated than traditional CAR-Ts, as no patients experienced cytokine release syndrome or any adverse effects. This is likely because where DNA results in permanent cell changes that can be replicated, mRNA induced changes cannot, and as such result in more predictable pharmacokinetics and an improved safety profile.

CRISPR approved therapeutics? We’ve discussed CRISPR technology before but revisit it now following NewScientists deep dive. Whilst we agree that first generation CRISPR has the potential to tackle a number of diseases, ranging from “cancer to infertility”. Our (slight) concern with CRISPR stems from the off-target DNA modification (some studies quoting >50%), and with just one mutation needed to potentially cause disease, it’s clear that CRISPR could do with some finetuning. On a related topic, we are intrigued by base editing (‘CRISPR 2.0’), which is currently being trialled in a stem cell treatment from Beam Therapeutics (Beam 101) where bases can be switched out without making any cuts in DNA and this ultimately reduces the risk of unwanted mutations.

Other things in the news – other notable bits and pieces that caught our eye this week include Illumina's record fine from the EU ($432m for completing the acquisition of Grail with approval from Brussels) and looming changes in FDA adcomms (advisory committees which provide the FDA opportunity to get independent expert advice on a potential therapy). We can’t help but feel that there has been a bit of a sea-change since the pandemic when many a vaccine/therapy was approved vs previously (when the Adcomm platform could be a bit of grandstand for many leading scientists/clinicians to engage in some academic snobbery and find issue with new technologies/therapies). Adcomms are now being held less frequently (409 from 2010-2021) with 2021 being the alltime low with just 8 being held. Given that many ‘votes’ are also now flying through (eg Leqembi with a unanimous vote) perhaps we can dispense with this bit, but it is important – we think – to have the perspectives captured for the benefit of the approval committees.

*must do better